Project Summary Currently, there are over 14 million confirmed cases of COVID-19 globally with over 3.7 million confirmed cases in the United States alone. One of the early presenting neurological symptoms of individuals who are critically ill from COVID-19 is altered mental status, or delirium. Delirium, defined as an acute disorder of attention and cognition, is a frequent, life-threatening clinical syndrome. Delirium has been linked to acceleration of cognitive decline, and may also be unmasking underlying vulnerability due to pre-existing dementia pathology in those who do not have dementia or are mildly impaired. In this application, we propose i) to identify baseline clinical risk factors and blood biomarkers that are associated with delirium (Specific Aim 1) and ii) to determine the association between clinical risk factors, blood biomarkers, and in-hospital delirium with future cognitive decline in patients with COVID-19 (Specific Aim 2). For this proposal, we will administer a battery of cognitive tests and self-reported measures by phone at 6 months following hospital discharge. Cognitive test results will be reviewed and adjudicated by investigators with expertise in cognitive assessments. Clinical risk factors and blood biomarkers of inflammation available through electronic health records will be used to determine the association between baseline predisposing factors and in-hospital delirium (Specific Aim 1). Then, the association between clinical risk factors, blood inflammatory biomarkers, occurrence of in-hospital delirium and cognitive outcome at 6 months will be determined (Specific Aim 1). This proposal will characterize potential blood biomarkers for in-hospital occurrence of delirium, which may allow cost-effective implementation of interventions to prevent delirium. Additionally, this proposal will allow preliminary data collection to help further our understanding of the cognitive domains most impacted by COVID-19. This, in turn, will inform our design of an efficient long-term follow-up study to reduce patient burden. Data from the proposed project will also allow identification of high-risk patients who may need earlier clinical intervention for cognitive problems.